The main objective of the proposed research is to develop through the study of the properties of ribonucleotide reductase a rational approach for the design of specific and potent, irreversible inhibitors of this enzyme. It is felt that this critical metabolic site should be exploited for the design of compounds which, by blocking ribonucleotide reductase, would be useful in the chemotherapy of neoplasms. Ehrlich tumor cells will be used as the source of the enzyme. BIBLIOGRAPHIC REFERENCES: Cory, J. G., Crumley, J. and Wilkinson, D.S., "Evidence for Role of Purine Nucleoside Phosphorylase in Sensitivity of Novikoff Hepatoma Cells to 5-Fluorouracil", Adv. Enz. Reg. 15 in press (1977). George, C.B. and Cory, J.G., "Metabolism of the Dialdehyde Derivative of Inosine (NSC-118994): Transport, Distribution and Incoporation into RNA of Ehrlich Tumor Cells", Biochem. Pharm. in press (1977).